Indanol diesters with thiocarbonic acid

ABSTRACT

New indanol diesters with thiocarbonic acid which have the formula   WHEREIN R and R1 each is hydrogen, lower alkyl, halo or trifluoromethyl are useful as fungistatic agents.

United States Patent Breuer INDANOL DIESTERS WITH THIOCARBONIC ACID [75]Inventor: Hermann Breuer, Regensburg,

Germany [73] Assignee: E. R. Squibb & Sons. Inc.,

Princeton, NJ.

[22] Filed: Apr. 11, 1974 [2] Appl. N0.: 460,007

[52] U.S. Cl. 260/455 B; 424/30l [51] Int. Cl. C07c 154/00 [58] Field ofSearch 260/455 B [56] References Cited UNITED STATES PATENTS.

3,637,790 1/1972 Truhcr et all. 260/455 B Primary E.\'aminerLewis GottsAssistant E.\'aminerD. R. Phillips Attorney, Agent, or Firm-Lawrence S.Levinson; Merle J. Smith 57 ABSTRACT New indanol diesters withthiocarbonic acid which have the formula wherein R and R, each ishydrogen, lower alkyl, halo or trifluoromethyl are useful as fungistaticagents.

8 Claims, N0 Drawings INDANOL DIESTERS WITH THIOCARBONIC ACID SUMMARY OFTHE INVENTION This invention relates to new indanol 0.0'-diesters withthiocarbonic acid which have the formula S (I) o-c-o J wherein R and R,are independently hydrogen or halo. especially chloro. Preferably R andR, are the same.

DETAILED DESCRIPTION OF THE lNVENTlON The compounds of formula I areproduced by reacting an unsubstituted or substituted indanol of theformula (III) with thiophosgene or with a thionocarbonic acid esterchloride of the formula in an inert organic solvent like chloroform inthe presence of a base like sodium hydroxide.

The new compounds of this invention are fungistatic agents usefulagainst infections caused by Dermatophytes such as 'I'riclwplrrmnmanrugrophylus and can be applied topically to the skin of an affectedanimal species such as mice, guinea pigs or the like in a conventionalvehicle such as cream, ointment or lotion at a concentration of about0.1 to 3 /z (by weight).

The following examples are illustrative of the invention.

EXAMPLE 1 A solution of l6.86 g. (0.1 mol.) of 7-chloro-4- indanol in 50ml. of 2N sodium hydroxide solution is added dropwise at 20 C. withvigorous stirring to a solution of 5.75 g. (0.05 mol.) of thiophosgenein 25 ml. of anhydrous chloroform. The mixture is stirred at roomtemperature for hours. The layers are separated, the chloroform layer iswashed twice with water, dried with calcium chloride and concentrated.14.9 g. of crude 7-chloro-4-indanol. 0,0'-diester with thioearbonic acidare obtained. The crude product is purified by recrystallizing twicefrom ethanol, yield 8.25 g.; m.p. l-l67C.

EXAMPLE 2 By substituting S-indanol for the 7-chloro-4-indanol in theprocedure of Example l. S-indanol. 0.0-diester with thiocarbonic acid isobtained. yield 63%; mp l46l48C.

EXAMPLE 3 By substituting 4-indanol for the 7-chloro-4-indanol in theprocedure of Example 1, 4-indanol, 0,0'-diester with thiocarbonic acidis obtained.

EXAMPLE 4 By substituting 7-chloro-5-indanol for the 7-chloro- 4-indanolin the procedure of Example 1, 7-chloro-5- indanol. 0,0'-diester withthiocarbonic acid is obtained.

EXAMPLE 5 By reacting chlorothioformic acid, 0, 2-indanyl ester with7-trifluoromethyl-5-indanol in Example 1, 7-trifluoromethyl-S-indanol,0,0'-diester with thiocarbonic acid is obtained.

EXAMPLE 6 By substituting 6-methyl-4-indanol for the 7-chloro- 4-indanolin the procedure of Examale l. 6-methyl-4- indanol. 0.0'-diester withthiocarbonic acid is obtained.

EXAMPLE 7 By substituting 6-bromo-4-indanol for the 7-chloro- 4-indanolin the procedure of Example 1, 6-bromo-4- indanol. 0.0'-diester withthiocarbonic acid is obtained.

What is claimed is:

l. A compound of the formula wherein R and R, each is hydrogen. loweralkyl. halo or trifluoromethyl.

2. A compound of the formula ll o c o wherein R and R, have the samemeaning as in claim 1.

3. A compound of the formula

1. COMPOUND OF THE FORMULA
 2. A compound of the formula
 3. A compound ofthe formula
 4. A compound as in claim 2 wherein R and R1 each ishydrogen or halo.
 5. A compound as in claim 3 wherein R and R1 each ishydrogen or halo.
 6. A compound as in claim 2 wherein R and R1 each ischloro.
 7. A compound as in claim 3 wherein R and R1 each is hydrogen.8. A compound as in claim 3 wherein R is hydrogen and R1 istrifluoromethyl.